P. Falciparum Infection Dynamics and Transmission to Inform Elimination (INDIE-1b)

London School of Hygiene and Tropical Medicine

Status: Unknown

Conditions: Malaria

Treatments: Other: Community Case Management; Other: Monthly malaria screening; Other: MDA; Other: Weekly fever screening and treatment

Study type: Interventional

Funder types: Other

Identifiers

NCT04053907

16642

OPP1173572 (Other Grant/Funding Number)

Details and patient eligibility

About

In the current study, three experimental approaches aiming at reducing malaria transmission will be tested. The study will cover two transmission season (2019 and 2020) and the interventions will vary by season. More specifically, in the 2019 transmission season (June-December) (Year 1), community case management of malaria (CCM) will be implemented in all eight villages as improved standard of care; in the 2020 transmission season (Year 2), the eight study villages will be divided into 4 study arms. CCM will continue in all villages; two villages will continue with CCM only (Arm 1, control); the three other pairs of villages will receive active fever screening and treatment (Arm 2); monthly mass screening and treatment (MSAT) (Arm 3); and mass drug administration (MDA) during the last 3 months of the dry season (April-June) (Arm 4). For MDA, the whole population (except for those not fulfilling the entry criteria) will be treated with a full course of dihydroartemisinin-piperaquine (DP) (320/40mg and 160/20mg piperaquine/ dihydroartemisinin per tablet) per manufacturer's guidelines (once daily for 3 days and according to body weight). The MDA treatment will be repeated 3 times at monthly intervals.

Full description

In the current study, the investigators will first improve access to care in all villages by implementing community-based clinical case management (CCM) (year 1). In this year, the investigators will quantify gametocyte carriage and transmission from clinical cases passively recruited by CCM, and gametocyte carriage and transmission from asymptomatic infections detected in community surveys. These data will support the interpretation of the main study outcomes in year 2 when the investigators will directly compare the effect of CCM on the human reservoir of infection as compared to three different approaches, namely i) active fever screening and treatment that should detect symptomatic infections for early treatment; ii) Mass Screening and Treatment (MSAT) that will systematically screen, using point-of-care diagnostics, the whole population, with infected individuals immediately treated; and iii) mass drug administration (MDA) that will treat the whole population with a full course of an antimalarial treatment.

Enrollment: 4,000 estimated patients

Sex: All

Ages: 6+ months old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Resident in the village.
2. Willingness to participate in repeated assessments of health and infection status and to donate a maximum of 30 mL (milliliter) of blood (children <5 years of age), 37 mL (milliliter) of blood (children <10 years of age) or 52 mL (milliliter) of blood (older individuals) during an 18-month period.

Exclusion criteria

1. Any chronic illness that would affect study participation.
2. Pre-existing severe chronic health conditions
3. History of intolerance to artemether-lumefantrine.
4. Participants < 6months old and pregnant women in the first trimester (only for Arm with MDA-DP treatment).
5. Hypersensitivity to DP (only for Arm with MDA-DP treatment).
6. Taking drugs that influence cardiac function or prolong QTcorrected interval (only for Arm with MDA-DP treatment).

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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4,000 participants in 4 patient groups

CCM:Standard of Care

No Intervention group

Description:

Community Case Management (CCM), with passively monitored malaria incidence by community health workers using standard RDTs and artemisinin-based combination therapy (ACT), artemether-lumefantrine (AL) according to national guidelines.

CCM plus weekly fever screening and treatment

Experimental group

Description:

CCM plus active case detection (ACD) by fever screening and treatment if positive. Trained village health workers (VHW) recruited for this study will carry out weekly visits of all residents and screen for fever using research-grade thermometers. A standard RDT will be performed in all individuals with a body temperature ≥37.5°C or with reported fever in the last 24 hours. RDT positive individuals will be treated with AL according to national guidelines.

Treatment:

Other: Weekly fever screening and treatment

Other: Community Case Management

CCM plus MSAT

Experimental group

Description:

CCM plus monthly screening for malaria infection and treatment of positive individuals, regardless of symptoms. Screening will be performed by research staff and timed to ensure a gap of 25-35 days between screening rounds; Positive individuals will be treated with AL, according to national guidelines.

Treatment:

Other: Monthly malaria screening

Other: Community Case Management

CCM plus dry season MDA

Experimental group

Description:

CCM plus plus 3 monthly rounds of MDA with a long-acting ACT (dihydroartemisinin-piperaquine, DP) starting in the dry season (April, May, June) (tablets of 320/40mg and 160/20mg piperaquine/ dihydroartemisinin per tablet. Administration of a full course of DP will be done as per manufacturer's guidelines once daily for 3 days and according to body weight).

Treatment:

Other: MDA

Other: Community Case Management